Photocatalytic degradation has emerged as a promising and sustainable solution to the rising environmental concerns caused by the emergence of pharmaceutical contaminants in aquatic bodies. Given its sustainability, nontoxicity, and energy-efficient attributes, extensive research has been conducted to investigate this approach and explore the synthesis of various photocatalysts. Metal–organic framework (MOF)-based nanocomposites exhibit a broad spectrum of applications across various fields due to their substantial surface area and versatile functionality. In these fields, MOF-based nanocomposites have proven to be excellent photocatalysts in water treatments, particularly in the breakdown of pharmaceutical pollutants in aquatic environments. This systematic review provides an overview of MOF-based nanocomposites and their applications in the photocatalytic degradation of pharmaceutical products. Several studies have explored different synthesis techniques for various MOF-based nanocomposites, and their degradation efficiencies against pollutants, under varying conditions such as catalyst loading, pollutant concentration, light intensity, and exposure time, among others, have also been reported. Moreover, modifications to these synthesis techniques have been made to enhance the degradation capability and stability of MOF-based nanocomposites. Meanwhile, the integration of other metals and biomaterials into MOF-based nanocomposites has been explored to improve the stability and recyclability of these photocatalysts. This paper also highlights the existing gaps in the current research to direct future investigations on photocatalytic degradation using MOF-based nanocomposites.